Prevalence of Alpha-1 Antitrypsin Deficiency in Poorly Controlled Asthma—Results from the ALA-ACRC Low-Dose Theophylline Trial

Eden, Edward; Holbrook, Janet T.; Brantly, Mark; Turino, Gerard M.; Wise, Robert A.

doi:10.1080/02770900701540028

Cited by 18 publications

(8 citation statements)

References 18 publications

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“…Asthma and acute bronchitis were the strongest clinical predictors of not carrying a homozygous deficiency. This confirms studies that did not report an increased prevalence of homozygous AATD in asthmatic patients [ 37 , 38 ].…”

Section: Discussionsupporting

confidence: 90%

Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015

Greulich

Nell

Herr

et al. 2016

Orphanet J Rare Dis

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BackgroundAlpha-1-antitrypsin deficiency (AATD) is an autosomal codominant inherited disease that is significantly underdiagnosed. We have previously shown that the combination of an awareness campaign with the offer of free diagnostic testing results in the detection of a relevant number of severely deficient AATD patients. The present study provides an update on the results of our targeted screening program (German AAT laboratory, University of Marburg) covering a period from August 2003 to May 2015.MethodsDiagnostic AATD detection test kits were offered free of charge. Dried blood samples were sent to our laboratory and used for the semiquantitative measurement of the AAT-level (nephelometry) and the detection of the S- or Z-allele (PCR). Isoelectric focusing was performed when either of the initial tests was indicative for at least one mutation. Besides, we evaluated the impact of additional screening efforts and the changes of the detection rate over time, and analysed the relevance of clinical parameters in the prediction of severe AATD.ResultsBetween 2003 and 2015, 18,638 testing kits were analysed. 6919 (37.12 %) carried at least one mutation. Of those, we identified 1835 patients with severe AATD (9.82 % of the total test population) including 194 individuals with rare genotypes. Test initiatives offered to an unselected population resulted in a dramatically decreased detection rate. Among clinical characteristics, a history of COPD, emphysema, and bronchiectasis were significant predictors for Pi*ZZ, whereas a history of asthma, cough and phlegm were predictors of not carrying the genotype Pi*ZZ.ConclusionA targeted screening program, combining measures to increase awareness with cost-free diagnostic testing, resulted in a high rate of AATD detection. The clinical data suggest that testing should be primarily offered to patients with COPD, emphysema, and/or bronchiectasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0453-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015

Greulich

Nell

Herr

et al. 2016

Orphanet J Rare Dis

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“…Four studies examined the role of targeted testing for A1AT deficiency in patients with asthma (21)(22)(23)(24). No study found an increased frequency in severe A1AT deficiency or abnormal alleles at the Pi locus compared with rates reported in control populations.…”

Section: Key Evidencementioning

confidence: 99%

Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

Marciniuk

Hernández²,

Balter³

et al. 2012

Canadian Respiratory Journal

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Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 µmol⁄L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.

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“…Many repeated articles and those with redundant content were eliminated. Finally, a total of 141 papers were selected . Where deemed appropriate, evidence‐based recommendations of the American College of Chest Physicians Task Force modified by the Canadian Thoracic Society COPD Clinical Assembly Alpha‐1 Antitrypsin Deficiency Expert Working Group were provided (Table ).…”

Section: Methodology Used For the Current Reviewmentioning

confidence: 99%

“…Although it is likely that AAT deficiency can promote the development of bronchial asthma and bronchiectasis , there is no reliable evidence as to whether AAT deficiency influences the frequency or gravity of these diseases . AAT‐deficiency‐related lung emphysema is characterized by early onset at 35–45 years, with chronic, progressive fatigue and other nonspecific respiratory symptoms.…”

Section: Clinical Expression Of Aat Deficiencymentioning

confidence: 99%

Role of alpha‐1 antitrypsin in human health and disease

2014

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Alpha‐1 antitrypsin (AAT) deficiency is an under‐recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000–1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000–10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad‐spectrum anti‐inflammatory, immunomodulatory, anti‐infective and tissue‐repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

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Prevalence of Alpha-1 Antitrypsin Deficiency in Poorly Controlled Asthma—Results from the ALA-ACRC Low-Dose Theophylline Trial

Cited by 18 publications

References 18 publications

Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015

Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015

Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

Role of alpha‐1 antitrypsin in human health and disease

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